Acanthamoeba keratitis is an infrequent, progressive, and often severe infection of healthy young adults, predominantly occurring as a complication of soft contact lens wear or minor corneal injury. Current medical therapy is unsatisfactory, and many eyes require therapeutic penetrating keratoplasty for elimination of the organism. The basis for medical failure has not been fully determined but may relate to the complex morphogenesis of the organism and the resistance of the trophozoite and cyst to the normal host defenses and to currently available antiamebic agents. The purpose of this study is to determine the optimal medical therapy of amebic keratitis. We will utilize an established rat model to assess the role of different species, strain variation, stage of cellular morphogenesis, and cell viability on the pathogenesis of Acanthamoeba keratitis. Susceptibility of Acanthamoeba species to selected antimicrobial compounds and other agents will be determined in static and dynamic broth systems. Based on in vitro activity, single and combined topically applied antiamebic agents will be assessed for efficacy in the rat model of keratitis. In addition, the roles of topical corticosteroids and host immune responses will be determined in treated and untreated infections. These studies should provide important new information of the pathogenesis of Acanthamoeba infection and serve as the basis for clinical studies on the management of Acanthamoeba keratitis.